tbuckley/cabot-search huggingface dataset:
Irradiation combined with PD-1 inhibitor aggravates immune-related pneumonitis of the non-irradiated lung in a preclinical model.
Authors: Xiaoxia Zhu, Simiao Qiao, Xuejiao Liao
Journal: Journal of Clinical Oncology (2022)

e14569 Background: The combination of radiation with PD-1 inhibitors for lung cancer is a trend. However, the combination is limited by immune-related adverse effects, particularly checkpoint inhibitor pneumonitis (CIP). The incidence and the mechanism of CIP of the non-irradiated lung caused by radiation plus PD-1 inhibitors remain unknown. This study was designed to evaluate the incidence of CIP and lung tissue morphology in the preclinical model induced by radiation combined with a PD-1 inhibitor (αPD-1). Methods: Fifty-four C57BL/6 mice were divided randomly into the normal group, the irradiation combined with the αPD-1 group (RT + αPD-1 group), and the single irradiation group (RT group). Mice in the RT + αPD-1 group were treated with right lung irradiation (8 Gy once) on day1 and anti-mouse PD-1 monoclonal antibody three times a week. Mice in the RT group received right lung irradiation alone. The mice were euthanized on day10, day15, and day20 after the end RT. Lung tissue morphology and pathological changes were assessed by hematoxylin-eosin staining. Lung fibrosis was evaluated by Masson staining and analysis of hydroxyproline. Results: Histopathological examination revealed that the inflammation in the irradiated lung is more severe than the unirradiated site. With the extension of time, the lung inflammation of mice in the RT group and RT + αPD-1 group was significantly aggravated, and the whole lung fibrosis appeared on day20. Inflammatory infiltrate scores, alveoli deformation scores, collagen volume fractions, and hydroxyproline contents in lung tissues were all significantly higher in mice administered αPD-1 plus irradiation than in the other groups. In particular, the inflammation is significantly worse in the unirradiated site of the mice administered PD-1 inhibitor plus irradiation than in the RT group on day15 and day20. Conclusions: Radiotherapy combined with PD-1 inhibitors could aggravate CIP on both sides. Further studies on the mechanism are under investigation. Our findings highlight the potential risk of CIP in non-irradiated lung in patients treated with radiotherapy and PD-1 inhibitors. Research Sponsor: This work was supported by the National Natural Science Foundation of China [No. 81972853, No. 81572279] and Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2019ZD009).
Hereditary cancer screening at an urban safety net hospital.
Authors: Sydney Brehany, Meryl D. Colton, Cassandra Duarte, Michael Baliton, Sonia Okuyama Sasaki
Journal: Journal of Clinical Oncology (2022)

10604 Background: Individuals with hereditary cancer syndromes (HCS) have a high lifetime risk of developing cancer. However, the rate at which at-risk individuals undergo genetic evaluation is low, particularly for individuals that belong to populations that are historically underserved. We sought to characterize the demographic factors that may be associated with receipt of recommended HCS evaluation and follow-up. Methods: All patients with pathologically confirmed breast, ovarian, or fallopian tube cancers and qualifying for hereditary breast and ovarian cancer (HBOC) testing based on NCCN guidelines from 2016 to 2021 at an urban safety-net hospital were included in this analysis. Institutional review board approval was obtained. Demographic and oncologic data, as well as HBOC genetic testing outcomes were collected through retrospective chart review using a standardized data collection tool. Univariate logistic regression models were constructed to test the association of variables with receiving hereditary cancer genetic testing. Results: A total of 312 patients were included in the analysis, 90% of which had breast cancer. Forty percent were non-English speaking, 31% were non-White, and 25% were uninsured. Overall, 70% of patients were referred for genetic counseling and 65% underwent testing. Our analysis showed higher association of genetic testing uptake with Spanish language [odds ratio (95% confidence interval)] [1.74 (1.04, 2.93)], stage II disease [2.15 (1.11, 4.16)], and having a referral to genetic counseling [9.21 (5.32, 15.96)]. A lower rate of genetic testing was associated with patients identifying as Black [0.36 (1.87, 0.70)], having Medicare insurance [0.29 (0.14, 0.61)], a higher Charlson Comorbidity Index [0.31 (0.13, 0.73)], and older age [0.94 (0.92, 0.96)]. Uninsured patients had a similar association with genetic testing uptake as patients with Medicaid. Variables seeming to have no association with genetic testing uptake include family history of cancer, type of cancer, performance status, substance use, and Latinx ethnicity. A pathologic variant was found in 13% of our population. A variant of unknown significance (VUS) was found in 33% of Hispanic or Latinx patients and in 46% of non-Hispanic or Latinx patients who received testing, for a combined VUS prevalence of 39%. Conclusions: Our analysis shows that genetic testing rates for patients meeting HBOC syndrome criteria at an urban, safety-net institution were higher than expected, particularly for Spanish speaking patients and those with Medicaid or no insurance. We hypothesize this may be due to the emphasis our institution places on the care of uninsured patients through programs to make services accessible, as well as strong engagement with the Spanish speaking community. These results can help guide future interventions to target patient groups with lower rates of genetic testing, as well as maintain the successes seen among our diverse population.
Use of systemic cancer treatments based on a validated survival prediction model in metastatic cancer.
Authors: Mohana Roy, Michael F. Gensheimer, Daniel Tandel Chang, Surbhi Singhal, Ali Raza Khaki
Journal: Journal of Clinical Oncology (2022)

e13515 Background: Use of systemic anti-cancer treatment near the end of life (EOL) is recognized as a low value practice with limited benefit to patients. Machine learning (ML) models that identify patients in close proximity to death can help prospectively assess oncology practice of systemic therapy use. We hypothesized that systemic therapy use would be higher based on predicted survival compared with actual survival. Methods: We calculated prevalence of systemic therapy use based on predicted and actual survival among patients with metastatic cancer at Stanford Healthcare from 2008-2019. Patients were included if they were in the test set of the ML model, had an eligible outpatient oncology clinic visit for which a predicted survival was calculated and were deceased . Median predicted survival was calculated from the ML model at each outpatient oncology visit and treatment was linked to a visit date if within 14 days of each other. Prevalence of systemic therapy was calculated for patients with a predicted or actual survival of &lt; 6 months, 6-12 months, 12-18 months and 18-24 months. The five categories of treatment were: chemotherapy, targeted/antibody, hormone, immunotherapy, and other. Results: A total of 951 deceased patients who received anticancer treatment are included and a total of 21,283 doses of treatment were administered with a mean of 22 doses per patient. The median age at metastatic cancer diagnosis was 58 years, 53% of patients were female and most patients identified as White (55%) or Asian (23%). The most common disease groups were gastrointestinal (21.6%), thoracic (18.6%) and breast (14.9%). Overall, the use of different treatment types did not differ based on either predicted or actual survival (Table). In all the survival groupings, chemotherapy remained the predominant medication type, however with a trend of decreasing use with longer predicted and actual survival. Conclusions: The use of cancer medications and the type of medication given did not change based on predicted or actual survival in a large group of patients with metastatic cancer. There was a trend of decreasing chemotherapy use with longer prognosis. Further investigation into use in time intervals closer to (predicted or actual) death and inclusion of those who did not receive any systemic therapy are underway.[Table: see text]
Thymoma and pure red cell aplasia: A single institution experience.
Authors: Tara Seibert, Patrick J. Loehrer, Andrew O'Brien
Journal: Journal of Clinical Oncology (2022)

e20625 Background: Thymoma is an uncommon malignancy often associated with paraneoplastic syndromes including pure red cell aplasia (PRCA), occurring in up to 5% of patients with thymoma. Considering the rarity of thymoma-associated PRCA, optimal treatment regimens and impact on thymoma disease course have yet to be established. Methods: A retrospective chart review was conducted for patients seen at the IUSCCC with thymoma and PRCA to extract and synthesize data on patient demographics, thymoma histology, hemoglobin levels, timeline of diagnoses, treatment regimens, and outcomes. Results: From 1993 to 2022, 10 patients (M:F = 4:6) with thymoma and PRCA were identified. Median follow-up duration was 75.0 months (range 32-202). Median age at thymoma diagnosis was 53.5 (range 40-80). Median age at PRCA diagnosis was 64.0 (range 40-80). Mean hemoglobin at PRCA diagnosis was 6.6. WHO classifications of thymoma included 10.0% A, 40.0% B1, 10.0% B2, 10.0% B2/B3, 30.0% not otherwise specified. Masoaka stages of thymoma included 20.0% stage I, 10.0% stage II, 10.0% stage III, 30.0% stage IVA, 30.0% stage IVB. Patients initially presented with thymoma (n = 7), PRCA (n = 1), or concurrent thymoma and PRCA (n = 2). For those initially presenting with thymoma, PRCA was subsequently diagnosed after a median 19.5 months (range 9-144). Of these 7 patients 3 experienced a relapse or progression of their thymoma at time of PRCA diagnosis, 3/7 had stable disease (1-insufficient data). Additional paraneoplastic syndromes were seen in 6 patients (hypogammaglobulinemia-2; pure white cell aplasia-1; myasthenia gravis-1; autoimmune neutropenia-1; colitis -1). Other diminished immunologic parameters observed were: immunoglobulin levels (n = 3); CD4 counts (n = 2); CD4:CD8 ratio (n = 4); and total B cell (n = 6). The primary outcome of the study was transfusion dependence, defined as requiring ≥1 PRBC transfusion per month for ≥3 months. Six achieved transfusion independence, while 3 remained transfusion dependent despite therapy (1 LTFU). Both patients with concurrent thymoma and PRCA underwent thymectomy, but only one achieved transfusion independence with additional adjuvant immunosuppressive therapies. Median duration of transfusion independence was 18.5 months (range 4-204). Median survival after bone marrow biopsy diagnosis of PRCA was 50.0 months (range 9-202). Conclusions: The impact of PRCA on thymoma disease course is variable. Most patients will recover with immunosuppressive therapy, but approximately 30.0% patients remained transfusion dependent. Our experience does not support thymectomy alone as primary treatment of PRCA. More research is needed to evaluate the mechanism of developing PRCA in thymoma and to define the optimal therapeutic approach.
Outcomes of clostridioides difficile infection in patients with hematopoietic stem cell transplant.
Authors: Ratib Mahfouz, Mahmoud Mansour, Adham E. Obeidat, Mohammad Darweesh, Osama Batayneh, Ghulam Ghous
Journal: Journal of Clinical Oncology (2022)

e19054 Background: Hematopoietic stem cell transplantation (HSCT) recipients are at an increased risk for Clostridioides difficile infections (CDI). Despite it being the main cause of nosocomial enterocolitis in this group of patients, diagnosis of CDI remains challenging and carries significant morbidity and mortality. This is usually due to multiple comorbidities, recurrent antibiotics administration, prolonged immunosuppression, and lengthy hospitalization. This study aims to look more into outcomes and predictors of CDI in HSCT patients in terms of incidence, and mortality. Methods: The United States Nationwide Inpatient Sample was used to extract hospitalization data of patients admitted between 2016 to 2019. Using ICD10 revision codes, we identified adults with a discharge diagnosis of CDI and concomitant HSCT. The control group included non-HSCT patients with CDI. The primary outcome was in-hospital mortality. Secondary outcomes were the length of stay (LOS) and hospital charges. Additionally, predictors for developing CDI and dying from CDI were calculated in HSCT patients. Multivariate logistic regression was used to adjust for relevant variables. Results: An estimated 1,235,465 patients were admitted with CDI during the study period. CDI incidence per 100 discharges was higher among HSCT patients at 4.0% vs. 1.0% in the general population. After adjusting for comorbidities and demographic variables, HSCT was independently associated with increased odds of mortality (adjusted odds ratio [AOR] 1.47 (95%CI 1.20-1.80 and P &lt;0.01). Mean length of stay and hospital charges increased by 1.76 days (95%CI 0.90-2.62, P &lt; 0.01) and $59,023 (95%CI $35,940-$82,105, P &lt; 0.01), respectively, in the HSCT group. In the HSCT group, patients with severe liver disease, malnutrition, and graft vs. host disease showed a significantly higher incidence of CDI. Predictors of mortality of HSCT patients and CDI are outlined in the attached table. Conclusions: HSCT recipients are at an increased risk for CDI compared to general population. LOS, total hospital charge, and mortality rate were significantly higher. The risk of CDI was found to be significantly higher in patients with moderate to severe liver disease, graft vs host disease, and malnutrition. The odds of mortality were found to be the highest in patients older than 65 years and those with congestive heart failure, moderate to severe liver disease, graft vs host disease, or malnutrition.[Table: see text]
Changes in cancer-related mortality during the COVID-19 pandemic in the United States.
Authors: Jingxuan Zhao, Xuesong Han, Kimberly Miller, Zhiyuan Zheng, Leticia M. Nogueira, Farhad Islami, Ahmedin Jemal, K. Robin Yabroff
Journal: Journal of Clinical Oncology (2022)

6581 Background: The coronavirus disease 2019 (COVID-19) pandemic resulted in delayed medical care that may have led to increased death rates in 2020 among people with medical conditions such as cancer. This study examined changes in cancer-related mortality between 2019 and 2020. Methods: We used the US 2019-2020 Multiple Cause of Death database from the CDC WONDER to identify cancer-related deaths, defined as decedents with invasive or noninvasive cancer as a contributing cause of death (ICD-10 codes: C00-C97 and D00-D09). We compared age-standardized cancer-related annual and monthly mortality rates (per 100,000 person-years and person-months, respectively) in January-December 2020 (pandemic) versus January-December 2019 (pre-pandemic) overall and stratified by rurality and place of death. We calculated the 2020 excess death by comparing the numbers of observed death with the projected death based on age-specific cancer-related death rate from 2015 to 2019. Results: The number of cancer-related deaths was 686 054 in 2020, up from 664 888 in 2019, with an annual increase of 3.2%. Compared to the number of projected deaths for 2020 (666 286), the number of cancer-related excess deaths was 19 768 in 2020. Annual age-standardized cancer-related mortality rate (per 100,000 person-years) continuously decreased from 173.7 in 2015 to 162.1 in 2019, while it increased to 164.1 in 2020 (2020 vs 2019 rate ratio (RR): 1.013, 95% confidence interval (CI): 1.009 - 1.016). The cancer-related monthly mortality rate was higher in April 2020 (RR: 1.032, 95% CI: 1.020 – 1.044) when healthcare capacity was most challenged by the pandemic, subsequently declined in May and June 2020, and higher mortality rates were again observed each month from July to December 2020 compared to 2019. In large metropolitan areas, the largest increase in cancer-related mortality was observed in April 2020, while in non-metropolitan areas, the largest increases occurred from July to December 2020, coinciding with the time-spatial pattern of COVID-19 incidence in the country. Compared to 2019, cancer-related mortality rates were lower from March to December 2020 in medical facilities, hospice facilities, and nursing homes or long-term care settings but higher in decedent's homes. Conclusions: The COVID-19 pandemic led to significant increases in cancer-related deaths in 2020 versus 2019. Ongoing evaluation of the spatial-temporal effects of the pandemic on cancer care and outcomes is warranted, especially in relation to patterns in vaccine uptake and COVID-19 hospitalization rates.[Table: see text]
Characterization of mutational signatures of homologous recombination deficiency (HRD) in Chinese breast cancer.
Authors: Xiao Liu, Mingwei Li, Feng Lou, Shanbo Cao, Huina Wang
Journal: Journal of Clinical Oncology (2022)

e15129 Background: Homologous recombination deficiency (HRD) is a common molecular characteristic of genomic instability and has been proved to be an important biomarker for personalized therapy decisions and stratified management in breast cancer. In this study, we explored the mutational features of HRD tumors identified by HRD score in Chinese breast cancer. Methods: Tumor tissue DNA from 68 breast cancer patients was isolated and sequenced by next-generation sequencing (NGS) technologies with AcornMed 808-genes panel. HRD score was calculated as an unweighted sum of loss of heterozygosity (LOH) score, telomeric allelic imbalance (TAI) score and large-scale state transition (LST) score by AcornHRD algorithm, and mutations in 39 homologous recombination (HR) related genes including BRCA1/2 were identified for each case. Results: Based on the mutation alternation profiles from our cohort, somatic BRCA1/2 mutations were present in 15 patients (22.1%) while 29 patients (42.6%) harbored one or more mutations in HR-related genes excluding BRCA1/2. Germline mutations of BRCA1/2 and other HR-related genes occurred in 11.8% and 4.4% of cases detected, respectively.In our cohort, the median HRD score was 40 (range from 3 to 92). Sixty-eight cases were divided into HRD-high or HRD-low group based on a cut-off value of ≥ 42 or &lt; 42, with HRD-high group accounting for approximately 47% of our cohort, indicating the combination with HRD score yielded an increment of 26.5% in coverage of HRD within BRCA1/2 wildtype cases. The HRD-high group covered 82.4% of the BRCA-mutated cases and also showed higher mutation level of BRCA1/2-excluded HR genes than HRD-low group (p = 0.001). Prevalence of mutations in a total of 12 genes, including BRCA1(31.3% vs 5.6%, p = 0.009) and NBN (25% vs 5.6%, p = 0.038), were significant difference between HRD-high and HRD-low group. Besides, Cosmic Signature 1 (spontaneous deamination of 5-methylcytosine) and 5 (unknown) were existed in both groups, whereas Signature 6 (defective DNA mismatch repair) was only discovered in HRD-high group. Compared with HRD-low ones, copy number variations ratio was higher in HRD-high group (p = 0.031). Meanwhile, the patients with ERBB2 amplification (HER2+) showed a lower level of HRD score than HER2- ones. Conclusions: This study comprehensively delineated the genetic characteristics of HRD tumors, which suggests that HRD status marked by HRD score is strongly associated with BRCA1/2 and HR-related genes mutation as well as other genomic instability signatures, thus indicating its predictive value as a promising biomarker for DNA repair deficiency related drugs or therapies in Chinese breast cancer.
Historical redlining and breast cancer survival in the United States: Evidence from the 2010-2017 SEER Medicare linked dataset.
Authors: Jean C. Bikomeye, Yuhong M. Zhou, Emily L. McGinley, Bethany Canales, Tina W.F. Yen, Kirsten M. M. Beyer
Journal: Journal of Clinical Oncology (2022)

1095 Background: Cancer is the second leading cause of morbidity and mortality in the US. Systemic racism is a critical cause of health disparities and historically disadvantaged people experience poor outcomes including poor breast cancer (BC) survival. This study aims to investigate the impact of historical redlining on all-cause and BC-specific survival among older women in the US. Methods: Historic 1930’s Homeowner’s Loan Corporation (HOLC) boundaries and grades were linked to 2010 Census tracts and the 2010-2017 SEER Medicare BC cohort. Women were included if they were 66+ years old at diagnosis, diagnosed with invasive BC, enrolled in Medicare Part A and Part B for 12 months prior to diagnosis to calculate comorbidity, and a Census tract match for HOLC grade. The independent variable was HOLC grade in two categories: A and B(not redlined), and C and D(redlined). The outcomes were all-cause and BC-specific survival, determined by Kaplan Meier Survival curves and both unadjusted and adjusted Cox regression models. End point for censoring was 12/31/2019 (all-cause) and 12/31/2018 (BC-specific). The final models were stratified by age and tumor stage at diagnosis; and adjusted for comorbidity, race and ethnicity, hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, and interaction term between comorbidity and race. Results: Among 10,113 women, 62.8% resided in historically redlined Census tracts. At a mean (+SD) follow-up time of 48.5 (+28.8) months, 28.9% were deceased; 41.6% of which died of BC. Women residing in historically redlined census tracts experienced poorer BC survival (49.8 +28.2 months) than those residing in non-redlined Census tracts (57.8 +30.7 months). After controlling for covariates, residing in a historically redlined Census tract remained an independent predictor of higher mortality: HR (95%CI) = 1.11 (1.02, 1.20) and 1.24 (1.011, 1.39) for all-cause mortality and BC-specific mortality, respectively. Conclusions: Residing in a formerly redlined Census tract at the time of BC diagnosis is associated with worse all-cause and BC-specific mortality, even after stratifying/adjusting for important patient and tumor characteristics. Public health and government agencies stakeholders should consider historical contexts when designing and implementing equity-focused community and clinical interventions targeted at mitigating and reducing BC disparities and improving health equity.